This research is designed to investigate the role played by drug receptor sites in regulating the proliferation and differentiation of the hemopoietic stem cell. The study seeks to uncover receptor sites that switch DNA synthesis on or off in hemopoietic cells. Any role played by drug receptors in the leukemogenic process, in adverse effects on bone marrow of clinically useful drugs, and in immune reactions, specifically the graft versus host reaction, will be studied. The phosphodiesterase enzymes vary in their sensitivty to a particular inhibitor. By investigating a variety of agents that inhibit phosphodiesterase, an attempt will be made to manipulate the cell cycle in tissues such as bone marrow. Such manipulation of the cell cycle may be a means of altering the sensitivity of tissues to cycle-dependent anticancer agents or cycle-dependent drugs used in immunosuppressive treatment. Hence, attempts will made to promote a more selective action of cytotoxic drugs on specific tissues. It is not known whether drug receptors play a direct role in the anti-proliferative action of cytotoxic agents. Studies will be made designed to determine whether previous blocking of receptor sites (without alteration of the cell cycle state) would modify the cell-killing action of such compounds. BIBLIOGRAPHIC REFERENCES: Cholinergic Mechanisms and the Hemopoietic Stem Cell, Byron, J.W.; In: Erythropoiesis, Univ. of Tokyo Press; Ed: Makao, Fisher and Takaku, pp. 141-149, 1975.